This research will investigate the proposed link between exposure cells to extremely low frequency (elf) electromagnetic (EM) fields and malignancy. The major aim is to determine whether elf EM field exposure at 60 Hz can play a role in initiating, or augmenting neoplastic disease. The ramifications of this research have bearing on the general safety of exposure to EM fields in industrial and everyday life. Aim 1. To determine how the expression of cellular proto-oncogenes is altered in human cells exposed to elf EM fields by measurement of levels of mRNA transcripts and resulting proteins. Short exposures (1 to 60 min.) to defined elf EM fields will be used in initial experiments; further experiments will determine how the time course or other parameters of exposure affect mRNA levels. Aim 2. To investigate the role of signal transduction in cell response to elf EM fields; can a relation with signal transduction be made as predicted on the basis of previous studies? Transcripts of two transcription factors, c-myc and c-fos, are consistently increased in cells exposed to EM fields, and this response forms the basis for the proposed research. The experiments will determine if the time of response of the cell relative to induction of these transcripts following EM field exposure is consistent with other types of experiments where inductive agents are used. Second, each of the promotor region for these two genes will be transfected into human cells as a CAT construct to identify the specific sequence element(s) responsible for the induction. Preliminary experiments which have investigated the role of the "complete" c-myc promotor show that exposure of cells containing the transfected c-myc promotor to an elf EM field (B field =80muT; E field= 100 muV/m) for 20 minutes results in a significant increase in CAT expression.